The 50 most-cited articles in Annals of Internal Medicine, 2018

Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation. The checklist was developed by a 24-member expert panel and 2 research leads following published guidance from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. The final checklist contains 20 essential reporting items and 2 optional items. The authors provide a rationale and an example of good reporting for each item. The intent of the PRISMA-ScR is to help readers (including researchers, publishers, commissioners, policymakers, health care providers, guideline developers, and patients or consumers) develop a greater understanding of relevant terminology, core concepts, and key items to report for scoping reviews.

Clinical prediction models combine multiple predictors to estimate risk for the presence of a particular condition (diagnostic models) or the occurrence of a certain event in the future (prognostic models). PROBAST (Prediction model Risk Of Bias ASsessment Tool), a tool for assessing the risk of bias (ROB) and applicability of diagnostic and prognostic prediction model studies, was developed by a steering group that considered existing ROB tools and reporting guidelines. The tool was informed by a Delphi procedure involving 38 experts and was refined through piloting. PROBAST is organized into the following 4 domains: participants, predictors, outcome, and analysis. These domains contain a total of 20 signaling questions to facilitate structured judgment of ROB, which was defined to occur when shortcomings in study design, conduct, or analysis lead to systematically distorted estimates of model predictive performance. PROBAST enables a focused and transparent approach to assessing the ROB and applicability of studies that develop, validate, or update prediction models for…

Prediction models in health care use predictors to estimate for an individual the probability that a condition or disease is already present (diagnostic model) or will occur in the future (prognostic model). Publications on prediction models have become more common in recent years, and competing prediction models frequently exist for the same outcome or target population. Health care providers, guideline developers, and policymakers are often unsure which model to use or recommend, and in which persons or settings. Hence, systematic reviews of these studies are increasingly demanded, required, and performed. A key part of a systematic review of prediction models is examination of risk of bias and applicability to the intended population and setting. To help reviewers with this process, the authors developed PROBAST (Prediction model Risk Of Bias ASsessment Tool) for studies developing, validating, or updating (for example, extending) prediction models, both diagnostic and prognostic. PROBAST was developed through a consensus process involving a group of experts in the field. It…

Machine learning is used increasingly in clinical care to improve diagnosis, treatment selection, and health system efficiency. Because machine-learning models learn from historically collected data, populations that have experienced human and structural biases in the past-called protected groups-are vulnerable to harm by incorrect predictions or withholding of resources. This article describes how model design, biases in data, and the interactions of model predictions with clinicians and patients may exacerbate health care disparities. Rather than simply guarding against these harms passively, machine-learning systems should be used proactively to advance health equity. For that goal to be achieved, principles of distributive justice must be incorporated into model design, deployment, and evaluation. The article describes several technical implementations of distributive justice-specifically those that ensure equality in patient outcomes, performance, and resource allocation-and guides clinicians as to when they should prioritize each principle. Machine learning is providing…

Background: Opioid overdose survivors have an increased risk for death. Whether use of medications for opioid use disorder (MOUD) after overdose is associated with mortality is not known. Objective: To identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality. Design: Retrospective cohort study. Setting: 7 individually linked data sets from Massachusetts government agencies. Participants: 17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014. Measurements: Three types of MOUD were examined: methadone maintenance treatment (MMT), buprenorphine, and naltrexone. Exposure to MOUD was identified at monthly intervals, and persons were considered exposed through the month after last receipt. A multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality. Results: In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9…

Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune disease characterized by painful, swollen joints that can severely impair physical function and quality of life. The presenting symptoms of musculoskeletal pain, swelling, and stiffness are common in clinical practice, so familiarity with diagnosing and managing RA is crucial. Patients with RA are at greater risk for serious infection, respiratory disease, osteoporosis, cardiovascular disease, cancer, and mortality than the general population. In recent years, early diagnosis, aggressive treatment, and expanded therapeutic options of disease-modifying antirheumatic drugs have markedly improved both the management and long-term prognosis of RA.

Social determinants of health are nonmedical factors that can affect a person's overall health and health outcomes. Where a person is born and the social conditions they are born into can affect their risk factors for premature death and their life expectancy. In this position paper, the American College of Physicians acknowledges the role of social determinants in health, examines the complexities associated with them, and offers recommendations on better integration of social determinants into the health care system while highlighting the need to address systemic issues hindering health equity.

Description: In November 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) released a clinical practice guideline for the prevention, detection, evaluation, and treatment of high blood pressure (BP) in adults. This article summarizes the major recommendations. Methods: In 2014, the ACC and the AHA appointed a multidisciplinary committee to update previous reports of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The committee reviewed literature and commissioned systematic reviews and meta-analyses on out-of-office BP monitoring, the optimal target for BP lowering, the comparative benefits and harms of different classes of antihypertensive agents, and the comparative benefits and harms of initiating therapy with a single antihypertensive agent or a combination of 2 agents. Recommendations: This article summarizes key recommendations in the following areas: BP classification, BP measurement, screening for secondary hypertension, nonpharmacologic therapy, BP thresholds and cardiac risk…

Background: Computer-aided diagnosis (CAD) for colonoscopy may help endoscopists distinguish neoplastic polyps (adenomas) requiring resection from nonneoplastic polyps not requiring resection, potentially reducing cost. Objective: To evaluate the performance of real-time CAD with endocytoscopes (×520 ultramagnifying colonoscopes providing microvascular and cellular visualization of colorectal polyps after application of the narrow-band imaging [NBI] and methylene blue staining modes, respectively). Design: Single-group, open-label, prospective study. (UMIN [University hospital Medical Information Network] Clinical Trial Registry: UMIN000027360). Setting: University hospital. Participants: 791 consecutive patients undergoing colonoscopy and 23 endoscopists. Intervention: Real-time use of CAD during colonoscopy. Measurements: CAD-predicted pathology (neoplastic or nonneoplastic) of detected diminutive polyps (≤5 mm) on the basis of real-time outputs compared with pathologic diagnosis of the resected specimen (gold standard). The primary end point was whether CAD with the stained mode…

Background: Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease. Purpose: To summarize the evidence on adverse events associated with CPIs in patients with cancer and preexisting autoimmune disease. Data Sources: MEDLINE, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through September 2017 with no language restrictions. Study Selection: Original case reports, case series, and observational studies describing patients with cancer and autoimmune disease who were receiving CPIs. Data Extraction: 2 reviewers independently extracted data and assessed the quality of reporting. Data Synthesis: 123 patients in 49 publications were identified; 92 (75%) had exacerbation of preexisting autoimmune disease, irAEs, or both. No differences in adverse events were observed in patients with active versus inactive disease. Patients receiving immunosuppressive therapy at initiation of CPI therapy seemed to have…

Background: Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use. Objective: To examine the incidence of these events in a cohort of transgender persons. Design: Electronic medical record-based cohort study of transgender members of integrated health care systems who had an index date (first evidence of transgender status) from 2006 through 2014. Ten male and 10 female cisgender enrollees were matched to each transgender participant by year of birth, race/ethnicity, study site, and index date enrollment. Setting: Kaiser Permanente in Georgia and northern and southern California. Patients: 2842 transfeminine and 2118 transmasculine members with a mean follow-up of 4.0 and 3.6 years, respectively, matched to 48 686 cisgender men and 48 775 cisgender women. Measurements: VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts. Results: Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk…

Description: The American College of Physicians developed this guidance statement to guide clinicians in selecting targets for pharmacologic treatment of type 2 diabetes. Methods: The National Guideline Clearinghouse and the Guidelines International Network library were searched (May 2017) for national guidelines, published in English, that addressed hemoglobin A1c (HbA1c) targets for treating type 2 diabetes in nonpregnant outpatient adults. The authors identified guidelines from the National Institute for Health and Care Excellence and the Institute for Clinical Systems Improvement. In addition, 4 commonly used guidelines were reviewed, from the American Association of Clinical Endocrinologists and American College of Endocrinology, the American Diabetes Association, the Scottish Intercollegiate Guidelines Network, and the U.S. Department of Veterans Affairs and Department of Defense. The AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument was used to evaluate the guidelines. Guidance Statement 1: Clinicians should personalize goals for glycemic control in…

Background: In response to adverse outcomes from prescription opioids, the Centers for Disease Control and Prevention (CDC) released the Guideline for Prescribing Opioids for Chronic Pain in March 2016. Objective: To test the hypothesis that the CDC guideline release corresponded to declines in specific opioid prescribing practices. Design: Interrupted time series analysis of monthly prescribing measures from the IQVIA transactional data warehouse and Real-World Data Longitudinal Prescriptions population-level estimates based on retail pharmacy data. Population size was determined by U.S. Census monthly estimates. Setting: United States, 2012 to 2017. Patients: Persons prescribed opioid analgesics. Measurements: Outcomes included opioid dosage, days supplied, overlapping benzodiazepine prescriptions, and the overall rate of prescribing. Results: The rate of high-dosage prescriptions (≥90 morphine equivalent milligrams per day) was 683 per 100 000 persons in January 2012 and declined by 3.56 (95% CI, -3.79 to -3.32) per month before March 2016 and by 8.00 (CI, -8.69 to -7.31)…

Research on assessing or managing medication adherence applies approaches from observational, interventional, and implementation science that spans many disciplines and demands coherent conceptualization, valid methods, appropriate analyses, and complete and accurate reporting. To ensure such reporting, the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) Medication Adherence Reporting Guideline (EMERGE) recommends standard reporting approaches based on an accepted taxonomy. This guideline is derived from a literature review, a reactive Delphi study with 26 medication adherence experts from many countries and disciplines, and feedback from ESPACOMP members. It is designed to supplement existing guidelines for health research reporting and is structured around 4 minimum reporting criteria and 17 items reflecting best reporting practice. By enhancing and harmonizing research reporting, EMERGE aims to advance research and, ultimately, patient outcomes.

Background: Contemporary data on the prevalence of e-cigarette use in the United States are limited. Objective: To report the prevalence and distribution of current e-cigarette use among U.S. adults in 2016. Design: Cross-sectional. Setting: Behavioral Risk Factor Surveillance System, 2016. Participants: Adults aged 18 years and older. Measurements: Prevalence of current e-cigarette use by sociodemographic groups, comorbid medical conditions, and states of residence. Results: Of participants with information on e-cigarette use (n = 466 842), 15 240 were current e-cigarette users, representing a prevalence of 4.5%, which corresponds to 10.8 million adult e-cigarette users in the United States. Of the e-cigarette users, 15% were never-cigarette smokers. The prevalence of current e-cigarette use was highest among persons aged 18 to 24 years (9.2% [95% CI, 8.6% to 9.8%]), translating to approximately 2.8 million users in this age range. More than half the current e-cigarette users (51.2%) were younger than 35 years. In addition, the age-standardized prevalence of e-cigarette use was…

Women comprise more than one third of the active physician workforce, an estimated 46% of all physicians-in-training, and more than half of all medical students in the United States. Although progress has been made toward gender diversity in the physician workforce, disparities in compensation exist and inequities have contributed to a disproportionately low number of female physicians achieving academic advancement and serving in leadership positions. Women in medicine face other challenges, including a lack of mentors, discrimination, gender bias, cultural environment of the workplace, imposter syndrome, and the need for better work-life integration. In this position paper, the American College of Physicians summarizes the unique challenges female physicians face over the course of their careers and provides recommendations to improve gender equity and ensure that the full potential of female physicians is realized.

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a selective update of the prior CKD-MBD guideline published in 2009. The guideline update and the original publication are intended to assist practitioners caring for adults with CKD and those receiving long-term dialysis. Methods: Development of the guideline update followed an explicit process of evidence review and appraisal. The approach adopted by the Work Group and the evidence review team was based on systematic reviews of relevant trials, appraisal of the quality of the evidence, and rating of the strength of recommendations according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Searches of the English-language literature were conducted through September 2015 and were supplemented with targeted searches through February 2017. Final modification of the guidelines was informed by a public review process…

Background: There has been a dramatic shift in use of bariatric procedures, but little is known about their long-term comparative effectiveness. Objective: To compare weight loss and safety among bariatric procedures. Design: Retrospective observational cohort study, January 2005 to September 2015. (ClinicalTrials.gov: NCT02741674). Setting: 41 health systems in the National Patient-Centered Clinical Research Network. Participants: 65 093 patients aged 20 to 79 years with body mass index (BMI) of 35 kg/m2 or greater who had bariatric procedures. Intervention: 32 208 Roux-en-Y gastric bypass (RYGB), 29 693 sleeve gastrectomy (SG), and 3192 adjustable gastric banding (AGB) procedures. Measurements: Estimated percent total weight loss (TWL) at 1, 3, and 5 years; 30-day rates of major adverse events. Results: Total numbers of eligible patients with weight measures at 1, 3, and 5 years were 44 978 (84%), 20 783 (68%), and 7159 (69%), respectively. Thirty-day rates of major adverse events were 5.0% for RYGB, 2.6% for SG, and 2.9% for AGB. One-year mean TWLs were 31.2% (95% CI, 31.1% to…

Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation). Design: Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649). Setting: Single center. Participants: 10 HCV D+/R- kidney transplant candidates older than 50 years with no available living donors. Intervention: Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation;…

Background: Women with a history of hypertensive disorders of pregnancy (HDP) are nearly twice as likely to develop cardiovascular disease (CVD) as those who are normotensive during pregnancy. However, the emergence of CVD risk factors after HDP is less well-understood. Objective: To identify associations between HDP and maternal CVD risk factors and chart the trajectory of risk factor development after pregnancy. Design: Observational cohort study. Setting: United States. Participants: 58 671 parous NHS II (Nurses' Health Study II) participants who did not have CVD or risk factors of interest at baseline. Measurements: Women were followed for self-reported physician diagnosis of chronic hypertension and hypercholesterolemia and confirmed type 2 diabetes mellitus (T2DM) from their first birth through 2013; mean follow-up ranged from 25 to 32 years across these end points. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs, with adjustment for prepregnancy confounders. Results: Compared with women who were normotensive during pregnancy, those with…

Background: The quick Sequential Organ Failure Assessment (qSOFA) has been proposed for prediction of mortality in patients with suspected infection. Purpose: To summarize and compare the prognostic accuracy of qSOFA and the systemic inflammatory response syndrome (SIRS) criteria for prediction of mortality in adult patients with suspected infection. Data Sources: Four databases from inception through November 2017. Study Selection: English-language studies using qSOFA for prediction of mortality (in-hospital, 28-day, or 30-day) in adult patients with suspected infection in the intensive care unit (ICU), emergency department (ED), or hospital wards. Data Extraction: Two investigators independently extracted data and assessed study quality using standard criteria. Data Synthesis: Thirty-eight studies were included (n = 385 333). qSOFA was associated with a pooled sensitivity of 60.8% (95% CI, 51.4% to 69.4%) and a pooled specificity of 72.0% (CI, 63.4% to 79.2%) for mortality. The SIRS criteria were associated with a pooled sensitivity of 88.1% (CI, 82.3% to 92.1%) and a pooled…

Background: The 2013 pooled cohort equations (PCEs) are central in prevention guidelines for cardiovascular disease (CVD) but can misestimate CVD risk. Objective: To improve the clinical accuracy of CVD risk prediction by revising the 2013 PCEs using newer data and statistical methods. Design: Derivation and validation of risk equations. Setting: Population-based. Participants: 26 689 adults aged 40 to 79 years without prior CVD from 6 U.S. cohorts. Measurements: Nonfatal myocardial infarction, death from coronary heart disease, or fatal or nonfatal stroke. Results: The 2013 PCEs overestimated 10-year risk for atherosclerotic CVD by an average of 20% across risk groups. Misestimation of risk was particularly prominent among black adults, of whom 3.9 million (33% of eligible black persons) had extreme risk estimates (<70% or >250% those of white adults with otherwise-identical risk factor values). Updating these equations improved accuracy among all race and sex subgroups. Approximately 11.8 million U.S. adults previously labeled high-risk (10-year risk ≥7.5%) by the 2013 PCEs would…

Background: Patients with myeloproliferative neoplasms (MPNs) are reported to be at increased risk for thrombotic events. However, no population-based study has estimated this excess risk compared with matched control participants. Objective: To assess risk for arterial and venous thrombosis in patients with MPNs compared with matched control participants. Design: Matched cohort study. Setting: Population-based setting in Sweden from 1987 to 2009, with follow-up to 2010. Patients: 9429 patients with MPNs and 35 820 matched control participants. Measurements: The primary outcomes were rates of arterial and venous thrombosis. Flexible parametric models were used to calculate hazard ratios (HRs) and cumulative incidence with 95% CIs. Results: The HRs for arterial thrombosis among patients with MPNs compared with control participants at 3 months, 1 year, and 5 years were 3.0 (95% CI, 2.7 to 3.4), 2.0 (CI, 1.8 to 2.2), and 1.5 (CI, 1.4 to 1.6), respectively. The corresponding HRs for venous thrombosis were 9.7 (CI, 7.8 to 12.0), 4.7 (CI, 4.0 to 5.4), and 3.2 (CI, 2.9 to 3.6). The rate…

Background: Drug use-associated infective endocarditis (DUA-IE) is increasing as a result of the opioid epidemic. Infective endocarditis may require valve surgery, but surgical treatment of DUA-IE has invoked controversy, and the extent of its use is unknown. Objective: To examine hospitalization trends for DUA-IE, the proportion of hospitalizations with surgery, patient characteristics, length of stay, and charges. Design: 10-year analysis of a statewide hospital discharge database. Setting: North Carolina hospitals, 2007 to 2017. Patients: All patients aged 18 years or older hospitalized for IE. Measurements: Annual trends in all IE admissions and in IE hospitalizations with valve surgery, stratified by patients' drug use status. Characteristics of DUA-IE surgical hospitalizations, including patient demographic characteristics, length of stay, disposition, and charges. Results: Of 22 825 IE hospitalizations, 2602 (11%) were for DUA-IE. Valve surgery was performed in 1655 IE hospitalizations (7%), including 285 (17%) for DUA-IE. Annual DUA-IE hospitalizations increased from 0.92 to…

Background: Organs from hepatitis C virus (HCV)-infected deceased donors are often discarded. Preliminary data from 2 small trials, including THINKER-1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), suggested that HCV-infected kidneys could be safely transplanted into HCV-negative patients. However, intermediate-term data on quality of life and renal function are needed to counsel patients about risk. Objective: To describe 12-month HCV treatment outcomes, estimated glomerular filtration rate (eGFR), and quality of life for the 10 kidney recipients in THINKER-1 and 6-month data on 10 additional recipients. Design: Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897). Setting: Single center. Participants: 20 HCV-negative transplant candidates. Intervention: Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir-grazoprevir on posttransplant day 3. Measurements: The primary outcome was HCV cure. Exploratory outcomes included 1) RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)…

Background: Prescription drug monitoring programs (PDMPs) are a key component of the president's Prescription Drug Abuse Prevention Plan to prevent opioid overdoses in the United States. Purpose: To examine whether PDMP implementation is associated with changes in nonfatal and fatal overdoses; identify features of programs differentially associated with those outcomes; and investigate any potential unintended consequences of the programs. Data Sources: Eligible publications from MEDLINE, Current Contents Connect (Clarivate Analytics), Science Citation Index (Clarivate Analytics), Social Sciences Citation Index (Clarivate Analytics), and ProQuest Dissertations indexed through 27 December 2017 and additional studies from reference lists. Study Selection: Observational studies (published in English) from U.S. states that examined an association between PDMP implementation and nonfatal or fatal overdoses. Data Extraction: 2 investigators independently extracted data from and rated the risk of bias (ROB) of studies by using established criteria. Consensus determinations involving all…

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. Most cases are diagnosed incidentally in the primary care or hospital setting on the basis of elevated liver enzyme levels or hepatic steatosis on imaging. NAFLD encompasses a wide spectrum: The vast majority of patients have nonprogressive nonalcoholic fatty liver, and a few of those develop progressive liver injury, inflammation, and fibrosis, a condition termed nonalcoholic steatohepatitis. Cardiovascular disease is the leading cause of death in patients with nonalcoholic fatty liver disease. Persons with nonalcoholic steatohepatitis have increased liver-related mortality. In the absence of regulatory agency-approved drugs, lifestyle modification and weight loss remain the cornerstones of NAFLD therapy.

Background: Persons living with HIV (PLWH) have an elevated risk for certain types of cancer. With modern antiretroviral therapy, PLWH are aging and cancer rates are changing. Objective: To project cancer incidence rates and burden (number of new cancer diagnoses) among adult PLWH in the United States through 2030. Design: Descriptive. Setting: HIV/AIDS Cancer Match Study to project cancer rates and HIV Optimization and Prevention Economics model to project HIV prevalence. Participants: HIV-infected adults. Measurements: Projected cancer rates and burden among HIV-infected adults in the United States by age during 2006 to 2030 for AIDS-defining cancer (ADC)-that is, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer-and certain types of non-AIDS-defining cancer (NADC). All other cancer types were combined. Results: The proportion of adult PLWH in the United States aged 65 years or older is projected to increase from 8.5% in 2010 to 21.4% in 2030. Age-specific rates are projected to decrease through 2030 across age groups for Kaposi sarcoma, non-Hodgkin lymphoma, cervical…

Background: Tobacco control efforts implemented in the United States since the 1960s have led to considerable reductions in smoking and smoking-related diseases, including lung cancer. Objective: To project reductions in tobacco use and lung cancer mortality from 2015 to 2065 due to existing tobacco control efforts. Design: Comparative modeling approach using 4 simulation models of the natural history of lung cancer that explicitly relate temporal smoking patterns to lung cancer rates. Setting: U.S. population, 1964 to 2065. Participants: Adults aged 30 to 84 years. Measurements: Models were developed using U.S. data on smoking (1964 to 2015) and lung cancer mortality (1969 to 2010). Each model projected lung cancer mortality by smoking status under the assumption that current decreases in smoking would continue into the future (status quo trends). Sensitivity analyses examined optimistic and pessimistic scenarios. Results: Under the assumption of continued decreases in smoking, age-adjusted lung cancer mortality was projected to decrease by 79% between 2015 and 2065. Concomitantly,…

Background: The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. Objective: To study the diagnostic utility of WES in a selected referral population of adults with CKD. Design: Observational cohort. Setting: A major academic medical center. Patients: 92 adults with CKD of unknown cause or familial nephropathy or hypertension. Measurements: The diagnostic yield of WES and its potential effect on clinical management. Results: Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the…

Background: The epidemic of drug overdose deaths in the United States has led to an increase in organ donors. Objective: To characterize donors who died of overdose and to analyze outcomes among transplant recipients. Design: Prospective observational cohort study. Setting: Scientific Registry of Transplant Recipients, 1 January 2000 to 1 September 2017. Participants: 138 565 deceased donors; 337 934 transplant recipients at 297 transplant centers. Measurements: The primary exposure was donor mechanism of death (overdose-death donor [ODD], trauma-death donor [TDD], or medical-death donor [MDD]). Patient and graft survival and organ discard (organ recovered but not transplanted) were compared using propensity score-weighted standardized risk differences (sRDs). Results: A total of 7313 ODDs and 19 897 ODD transplants (10 347 kidneys, 5707 livers, 2471 hearts, and 1372 lungs) were identified. Overdose-death donors accounted for 1.1% of donors in 2000 and 13.4% in 2017. They were more likely to be white (85.1%), aged 21 to 40 years (66.3%), infected with hepatitis C virus (HCV)…

Background: Lung cancer screening guidelines recommend using individualized risk models to refer ever-smokers for screening. However, different models select different screening populations. The performance of each model in selecting ever-smokers for screening is unknown. Objective: To compare the U.S. screening populations selected by 9 lung cancer risk models (the Bach model; the Spitz model; the Liverpool Lung Project [LLP] model; the LLP Incidence Risk Model [LLPi]; the Hoggart model; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 [PLCOM2012]; the Pittsburgh Predictor; the Lung Cancer Risk Assessment Tool [LCRAT]; and the Lung Cancer Death Risk Assessment Tool [LCDRAT]) and to examine their predictive performance in 2 cohorts. Design: Population-based prospective studies. Setting: United States. Participants: Models selected U.S. screening populations by using data from the National Health Interview Survey from 2010 to 2012. Model performance was evaluated using data from 337 388 ever-smokers in the National Institutes of Health-AARP Diet and…

Background: Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism (PE) are limited, and guidelines provide inconsistent recommendations on use of diagnostic tests. Objective: To prospectively validate a diagnostic strategy in pregnant women with suspected PE. Design: Multicenter, multinational, prospective diagnostic management outcome study involving pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and computed tomography pulmonary angiography (CTPA). (ClinicalTrials.gov: NCT00740454). Setting: 11 centers in France and Switzerland between August 2008 and July 2016. Patients: Pregnant women with clinically suspected PE in emergency departments. Intervention: Pulmonary embolism was excluded in patients with a low or intermediate pretest clinical probability and a negative D-dimer result. All others underwent lower limb CUS and, if results were negative, CTPA. A ventilation-perfusion (V/Q) scan was done if CTPA results were inconclusive. Pulmonary embolism was…

Much of what is formally taught in medicine is about the knowledge, skills, and behaviors required of a physician, including how to express compassion and respect for patients at the bedside. What is learned, however, includes not only admirable qualities but also behaviors and qualities that are inconsistent with ethics and professionalism. Positive role models may reinforce the character and values the profession seeks to cultivate; negative ones directly contradict classroom lessons and expectations of patients, society, and medical educators. These positive and negative lessons, which are embedded in organizational structure and culture, are the hidden curricula conveyed in medical schools, residency programs, hospitals, and clinics. This position paper from the American College of Physicians focuses on ethics, professionalism, and the hidden curriculum. It provides strategies for revealing what is hidden to foster the development of reflective and resilient lifelong learners who embody professionalism and clinicians who are, and are perceived as, positive role models. Making…

Letters20 November 2018Pregabalin and the Risk for Opioid-Related Death: A Nested Case–Control StudyTara Gomes, MHSc, PhD, Simon Greaves, MSc, Wim van den Brink, MD, PhD, Tony Antoniou, PharmD, PhD, Muhammad M. Mamdani, PharmD, MA, MPH, J. Michael Paterson, MSc, Diana Martins, MSc, and David N. Juurlink, MD, PhDTara Gomes, MHSc, PhDLi Ka Shing Knowledge Institute of St. Michael's Hospital, Institute for Clinical Evaluative Sciences, and University of Toronto, Toronto, Ontario, Canada (T.G., T.A., M.M.M.), Simon Greaves, MScInstitute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (S.G.), Wim van den Brink, MD, PhDAcademic Medical Center University of Amsterdam, Amsterdam, the Netherlands (W.V.), Tony Antoniou, PharmD, PhDLi Ka Shing Knowledge Institute of St. Michael's Hospital, Institute for Clinical Evaluative Sciences, and University of Toronto, Toronto, Ontario, Canada (T.G., T.A., M.M.M.), Muhammad M. Mamdani, PharmD, MA, MPHLi Ka Shing Knowledge Institute of St. Michael's Hospital, Institute for Clinical Evaluative Sciences, and University of Toronto, Toronto,…

Background: Long-term health risks for adults who donate kidneys are unclear. Purpose: To summarize evidence about mid- and long-term health risks associated with living kidney donation in adults. Data Sources: PubMed, Embase, Scopus, and PsycINFO without language restriction from April 1964 to July 2017. Study Selection: Observational studies with at least 1 year of follow-up that compared health outcomes in adult living kidney donors versus nondonor populations. Data Extraction: Two investigators independently extracted study data and assessed study quality. Data Synthesis: 52 studies, comprising 118 426 living kidney donors and 117 656 nondonors, were included. Average follow-up was 1 to 24 years. No evidence suggested higher risk for all-cause mortality, cardiovascular disease, hypertension, type 2 diabetes, or adverse psychosocial health outcomes in living kidney donors than in nondonor populations. Donors had higher diastolic blood pressure, lower estimated glomerular filtration rates, and higher risk for end-stage renal disease (ESRD) (relative risk [RR], 8.83 [95% CI, 1.02…

Background: Probiotics, prebiotics, and synbiotics are used increasingly, although the safety and potential harms of these interventions are poorly understood. Purpose: To examine how harms-related information is reported in publications of randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics. Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (without language restrictions) from 1 January 2015 to 20 March 2018. Study Selection: RCTs assessing the safety or efficacy of at least 1 intervention involving probiotics, prebiotics, or synbiotics alone or in combination with another intervention compared with any control (such as a placebo or an antibiotic) for any clinical condition. Data Extraction: 4 reviewers independently assessed study characteristics, the reporting of harms, and the presentation of safety results. Data Synthesis: Of 384 trials conducted in healthy volunteers (n = 136) or patients with any of several medical conditions (n = 248), 339 (88%) were published in specialty journals. Trials most often…

Background: Bariatric surgery improves glycemic control in patients with type 2 diabetes mellitus (T2DM), but less is known about microvascular outcomes. Objective: To investigate the relationship between bariatric surgery and incident microvascular complications of T2DM. Design: Retrospective matched cohort study from 2005 to 2011 with follow-up through September 2015. Setting: 4 integrated health systems in the United States. Participants: Patients aged 19 to 79 years with T2DM who had bariatric surgery (n = 4024) were matched on age, sex, body mass index, hemoglobin A1c level, insulin use, diabetes duration, and intensity of health care use up to 3 nonsurgical participants (n = 11 059). Intervention: Bariatric procedures (76% gastric bypass, 17% sleeve gastrectomy, and 7% adjustable gastric banding) compared with usual care. Measurements: Adjusted Cox regression analysis investigated time to incident microvascular disease, defined as first occurrence of diabetic retinopathy, neuropathy, or nephropathy. Results: Median follow-up was 4.3 years for both surgical and nonsurgical…

Background: The long-term effects of sigmoidoscopy screening on colorectal cancer (CRC) incidence and mortality in women and men are unclear. Objective: To determine the effectiveness of flexible sigmoidoscopy screening after 15 years of follow-up in women and men. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT00119912). Setting: Oslo and Telemark County, Norway. Participants: Adults aged 50 to 64 years at baseline without prior CRC. Intervention: Screening (between 1999 and 2001) with flexible sigmoidoscopy with and without additional fecal blood testing versus no screening. Participants with positive screening results were offered colonoscopy. Measurements: Age-adjusted CRC incidence and mortality stratified by sex. Results: Of 98 678 persons, 20 552 were randomly assigned to screening and 78 126 to no screening. Adherence rates were 64.7% in women and 61.4% in men. Median follow-up was 14.8 years. The absolute risks for CRC in women were 1.86% in the screening group and 2.05% in the control group (risk difference, -0.19 percentage point [95% CI, -0.49 to 0.11…

Background: Despite insufficient evidence regarding its risks and benefits, marijuana is increasingly available and is aggressively marketed to the public. Objective: To understand the public's views on the risks and benefits of marijuana use. Design: Probability-based online survey. Setting: United States, 2017. Participants: 16 280 U.S. adults. Measurements: Proportion of U.S. adults who agreed with a statement. Results: The response rate was 55.3% (n = 9003). Approximately 14.6% of U.S. adults reported using marijuana in the past year. About 81% of U.S. adults believe marijuana has at least 1 benefit, whereas 17% believe it has no benefit. The most common benefit cited was pain management (66%), followed by treatment of diseases, such as epilepsy and multiple sclerosis (48%), and relief from anxiety, stress, and depression (47%). About 91% of U.S. adults believe marijuana has at least 1 risk, whereas 9% believe it has no risks. The most common risk identified by the public was legal problems (51.8%), followed by addiction (50%) and impaired memory (42%). Among U.S. adults, 29.2%…

For more than 20 years, the American College of Physicians (ACP) has advocated for the need to address firearm-related injuries and deaths in the United States. Yet, firearm violence continues to be a public health crisis that requires the nation's immediate attention. The policy recommendations in this paper build on, strengthen, and expand current ACP policies approved by the Board of Regents in April 2014, based on analysis of approaches that the evidence suggests will be effective in reducing deaths and injuries from firearm-related violence.

Background: HIV infection is a persistent health concern in the United States, and men who have sex with men (MSM) continue to be the most affected population. Objective: To estimate HIV incidence and prevalence and the percentage of undiagnosed HIV infections overall and among MSM. Design: Cross-sectional analysis. Setting: National HIV Surveillance System. Participants: Persons aged 13 years or older with diagnosed HIV infection. Measurements: Data on HIV diagnoses and the first CD4 test result after diagnosis were used to model HIV incidence and prevalence and the percentage of undiagnosed HIV infections from 2008 to 2015 on the basis of a well-characterized CD4 depletion model. Results: Modeled HIV incidence decreased 14.8% overall, from 45 200 infections in 2008 to 38 500 in 2015, and among all transmission risk groups except MSM. The incidence of HIV increased 3.1% (95% CI, 1.6% to 4.5%) per year among Hispanic/Latino MSM (6300 infections in 2008, 7900 in 2015), decreased 2.7% (CI, -3.8% to -1.5%) per year among white MSM (8800 infections in 2008, 7100 in 2015), and remained…

Background: Many experts believe that hospitals with more frequent readmissions provide lower-quality care, but little is known about how the preventability of readmissions might change over the postdischarge time frame. Objective: To determine whether readmissions within 7 days of discharge differ from those between 8 and 30 days after discharge with respect to preventability. Design: Prospective cohort study. Setting: 10 academic medical centers in the United States. Patients: 822 adults readmitted to a general medicine service. Measurements: For each readmission, 2 site-specific physician adjudicators used a structured survey instrument to determine whether it was preventable and measured other characteristics. Results: Overall, 36.2% of early readmissions versus 23.0% of late readmissions were preventable (median risk difference, 13.0 percentage points [interquartile range, 5.5 to 26.4 percentage points]). Hospitals were identified as better locations for preventing early readmissions (47.2% vs. 25.5%; median risk difference, 22.8 percentage points [interquartile range, 17.9 to…

Clostridioides difficile (formerly Clostridium difficile) infection is the most frequently identified health care-associated infection in the United States. C difficile has also emerged as a cause of community-associated diarrhea, resulting in increased incidence of community-associated infection. Clinical illness ranges in severity from mild diarrhea to fulminant colitis and death. Appropriate management of infection requires understanding of the various diagnostic assays and therapeutic options as well as relevant measures to infection prevention. This article provides updated recommendations regarding the prevention, diagnosis, and treatment of incident and recurrent C difficile infection.

Letters18 December 2018Smoking, Vaping, and Use of Edibles and Other Forms of Marijuana Among U.S. AdultsStacey Steigerwald, MSSA, Peggy O. Wong, BA, Beth E. Cohen, MD, MAS, Julie H. Ishida, MD, MAS, Marzieh Vali, MS, Erin Madden, MS, and Salomeh Keyhani, MD, MPHStacey Steigerwald, MSSANorthern California Institute for Research and Education and San Francisco VA Medical Center, San Francisco, California (S.S., P.O.W., M.V., E.M.), Peggy O. Wong, BANorthern California Institute for Research and Education and San Francisco VA Medical Center, San Francisco, California (S.S., P.O.W., M.V., E.M.), Beth E. Cohen, MD, MASUniversity of California, San Francisco, and San Francisco VA Hospital, San Francisco, California (B.E.C., J.H.I., S.K.), Julie H. Ishida, MD, MASUniversity of California, San Francisco, and San Francisco VA Hospital, San Francisco, California (B.E.C., J.H.I., S.K.), Marzieh Vali, MSNorthern California Institute for Research and Education and San Francisco VA Medical Center, San Francisco, California (S.S., P.O.W., M.V., E.M.), Erin Madden, MSNorthern California Institute…

Background: More than 25 million adults in the United States have chronic pain. Chronic pain has been associated with suicidality, but previous studies primarily examined nonfatal suicidal behaviors rather than suicide deaths associated with chronic pain or the characteristics of such deaths. Objective: To estimate the prevalence of chronic pain among suicide decedents in a large multistate sample and to characterize suicide decedents with and without chronic pain. Design: Retrospective analysis of National Violent Death Reporting System (NVDRS) data. The NVDRS links death certificate, coroner or medical examiner, and law enforcement data collected by investigators, who often interview informants who knew the decedent to gather information on precipitating circumstances surrounding the suicide. Information is abstracted by using standard coding guidance developed by the Centers for Disease Control and Prevention. Setting: 18 states participating in the NVDRS. Participants: Suicide decedents with and without chronic pain who died during 1 January 2003 to 31 December 2014.…

Background: Treatment-free remission (TFR)-that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response-is an emerging treatment goal in chronic myeloid leukemia (CML). Objective: To evaluate TFR after discontinuation of second-line nilotinib therapy. Design: Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905). Setting: 63 centers in 18 countries. Patients: Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Interventions: Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1%) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01%) during TFR reinitiated nilotinib treatment. Measurements: Proportion of patients without loss of MMR, confirmed loss…

Background: Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes. Purpose: To evaluate associations between SCT and clinical outcomes in children and adults. Data Sources: English-language searches of PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase (1 January 1970 to 30 June 2018) and bibliographies of review articles. Study Selection: Observational controlled studies (published in English) in children or adults that examined an association between SCT and any of 24 clinical outcomes specified a priori in the following 6 categories: exertion-related injury; renal, vascular, pediatric, and surgery- or trauma-related outcomes; and overall mortality. Data Extraction: A single reviewer extracted study data, which was checked by another; 2 reviewers independently assessed study quality; and strength of evidence was assessed by consensus. Data Synthesis: Of 7083 screened studies, 41 met inclusion criteria. High-strength evidence supported a positive association between SCT and risk for…

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and are associated with increased morbidity and mortality risk. Purpose: To compare benefits and harms between catheter ablation and drug therapy in adult patients with AF and HF. Data Sources: ClinicalTrials.gov, PubMed, Web of Science (Clarivate Analytics), EBSCO Information Services, Cochrane Central Register of Controlled Trials, Google Scholar, and various scientific conference sessions from 1 January 2005 to 1 October 2018. Study Selection: Randomized controlled trials (RCTs) published in English that had at least 6 months of follow-up and compared clinical outcomes of catheter ablation versus drug therapy in adults with AF and HF. Data Extraction: 2 investigators independently extracted data and assessed study quality. Data Synthesis: 6 RCTs involving 775 patients met inclusion criteria. Compared with drug therapy, AF ablation reduced all-cause mortality (9.0% vs. 17.6%; risk ratio [RR], 0.52…

Falls are common among older adults. One in 3 adults aged 65 years or older and 1 in 2 adults aged 80 years or older fall each year. Interventions for prevention have been identified; however, they are often not addressed in primary care practice. Screening all older adults annually for falls can identify who will benefit from further clinical evaluation and management. Falls and the need for care from subsequent injury increase with age. They adversely affect quality of life and are a financial burden on the health care industry. As a result, risk reduction is a key focus of prevention efforts, even among very elderly persons.